Putting a brake on depression

About 10 to 20 per cent of depressed patients are resistant to conventional treatments, says Toronto neurosurgeon Andres Lozano.

Photograph by: Artem Furman
, Fotolia.com

Bruce Ross was depressed for nearly 40 years. "I’d had it since early high school," he says. "But this was the Seventies, and depression wasn’t really talked about, so I didn’t know what it was." Mr Ross, a gentle-voiced 53-year-old Canadian credit union executive, battled alone against his unknown enemy for two decades. He even tried moving home, 1,200 miles from Nova Scotia, to Chatham, Ontario, to shake off his mystery ailment. Nothing helped: "I found that my problems followed me wherever I went."

In the late Nineties, a doctor finally diagnosed clinical depression. Anti-depressants did not shift it, although he tried more than a dozen types; neither did psychotherapy, nor electroconvulsive therapy (ECT). By this time, he was married with a young daughter. "My psychiatrist said I was the most treatment-resistant patient he’d ever seen," he says, "although I’m not sure that’s a badge of honour." At one stage, Ross found himself on the fifth floor of a multi-storey car park, wondering whether it was time to end it all. "I don’t think I’d have ever gone through with it, but there were definitely times I thought about it."

Two years ago, Mr Ross learnt about a pioneering approach to treatment-resistant depression being trialled at the University of Toronto. Called deep brain stimulation (DBS), it involves inserting tiny electrodes, attached to a battery implanted below the collarbone, to target areas deep inside the brain. The electrodes act, loosely speaking, as a brain pacemaker, transmitting high frequency, continuous electrical impulses that, depending on where they are placed, can either inhibit or stimulate neural activity. Desperate for some relief, Mr Ross agreed to take part. "I wasn’t at all nervous," he says. "By that stage, I was pretty desperate. I just wanted it done."

DBS is already used for intractable Parkinson’s disease and also chronic pain. For intractable depression, the research is still at an early stage - but according to Prof Andres Lozano, the Toronto neurosurgeon who operated on Mr Ross, studies show it can improve symptoms in 60 per cent of such cases.

About 10 to 20 per cent of depressed patients are resistant to conventional treatments, he points out. "These patients are severely disabled," he says, "and at significant suicide risk."

Like all brain surgery, the operation is carried out while the patient is conscious, so that surgeons can be sure no brain damage is being inflicted. It involves drilling a half-inch hole in the skull and placing the electrodes in the target area. A battery is fitted just below the skin in a separate operation, with the lead connecting it to the electrodes running up the side of the neck to the head.

Prof Helen Mayberg, a neurologist at Emory University in Atlanta, Georgia, is one of the leading researchers in the field and carried out the first DBS on a patient with depression in 2005. In Parkinson’s, she says, researchers had identified the right target area: a motion circuit associated with structures called basal ganglia was found to be hyperactive, causing the typical symptoms of the disease, such as tremor. Blocking certain areas on this circuit with an electrical impulse was found to dampen down the circuit, and mitigate symptoms.

"We took the principle of the Parkinson’s treatment and applied it to depression," says Prof Mayberg. Years of medical imaging, she says, have shown several parts of the brain that are involved in mood disorders. "We hypothesised that a brain region called Area 25, which is part of the cingulate region, was the problem." Researchers experimented by using electricity to "turn down" activity in this area. "Same process as in Parkinson’s but a different spot."

"Area 25 is connected to areas related to sleep, motivation, reward and pleasure," adds Prof Lozano. "Think of your car. You have an accelerator but you also have a brake. Similarly, the brain has ’excitatory’ and ’inhibitory’ circuits. In depression, the sadness circuits are stuck on full throttle. We’re stimulating the inhibitory circuit, stepping on the brake."

And stepping on the brake seems to work. Far more research is needed, but the small studies that have been published - including the trial Mr Ross took part in, published recently in the Journal of Neurosurgery - "have built up a fairly substantial body of evidence" in its favour, according to Prof Mayberg. Of the 21 patients that took part, nearly two thirds had a 40 per cent or more reduction in symptoms at 12 months.

"With treatment of Area 25, if you get better, you stay better," says Prof Mayberg. And when it works, it’s dramatic, "like flipping a switch", according to Prof Lozano. The "million-dollar question", he says, is why some patients do not get better. "One possibility is that they have a different disease, that we call it depression but the basis of it is different. Another is that the brain wiring is different, that we’re not hitting the appropriate spot."

In the UK, researchers led by Dr Andrea Malizia, a psychiatrist at the University of Bristol, are looking at whether treating brain regions other than Area 25 might work for these non-responsive patients. "It’s far too early to say," he says, warning that the research is still unpublished, "but what we’ve found suggests that some people don’t respond to stimulation in one area and do respond to stimulation in another."

So far, the procedure has been carried out in just a few hundred patients with depression, but researchers hope it will become more widely used. "The costs of depression to an individual, to a family, to society, are considerable. No one wants unnecessary brain surgery, but if the procedure is shown to be safe, then it should be an option," says Prof Mayberg.

There are, of course, risks - including the possibility of the current spreading to neighbouring regions of the brain, causing side effects such as mania or panic - as have been seen in Parkinson’s patients. "If you make a hole in someone’s skull, there are risks," says Prof Mayberg. Dr Malizia also notes that DBS may be similar to some other treatments for depression, in which people become more motivated and energetic, but are still extremely depressed, making them a higher suicide risk.

Nevertheless, DBS represents a "paradigm shift" in thinking about depression and brain disorders, says Prof Mayberg. "We used to think of depression as a weakness of character, and thank God we got rid of that," she says. "Then we started thinking of it as a chemical imbalance. But your brain is not a bowl of soup, add salt and stir. It’s a wiring network of billions of neurons organised into units, choreographed, communicating with each other with exquisite precision. Now, we’re thinking in those terms." DBS for other conditions, such as obsessive-compulsive disorder and epilepsy, is also being investigated.

Two years in, Bruce Ross is delighted with the result. "Before the surgery, I’d have described my life as a four out of 10," he says. "Since then, I’d say I’m a seven. I don’t think I’ll ever be a nine or a 10, but is anybody? I sleep better, my appetite’s better. I feel more relaxed, I’m more motivated at work. Would I recommend it to others? Absolutely."

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